AJH
2005; 18:1528 –1533
Morning Blood Pressure Hyper-reactivity
Is an Independent Predictor for
Hypertensive Cardiac Hypertrophy
in a Community-Dwelling Population
Ruri Kaneda, Kazuomi Kario, Satoshi Hoshide,
Yuji Umeda, Yoko Hoshide, and Kazuyuki Shimada
Background: Morning blood pressure (BP) surge
seems to be a risk factor for cardiovascular events. Although physical activity after arising significantly affects
morning BP surge, it has remained unclear whether morning BP surge after controlling for physical activity (morning BP reactivity) is associated with target organ damage.
Methods: We performed ambulatory BP monitoring
with simultaneous actigraphy and echocardiography in
120 community-dwelling Japanese subjects. We determined the waking time by actigraphy, and defined morning BP surge (MBPS) as the average of systolic BP during
the 2 h after awakening minus the average of systolic BPs
during the 1 h that included the lowest sleep BP. The ratio
of MBPS/(sum of the 2-h physical activity after the arising
time)0.5 was calculated as the morning BP reactivity
(MBPR).
Results: In all the subjects studied (n ⫽ 120), MBPR
was positively associated with left ventricular (LV) mass
index (r ⫽ 0.30, P ⫽ .001). The MBPR had a positive
association with both 24-h BP variability (SD) (r ⫽ 0.373,
P ⬍ .001) and awake BP variability (r ⫽ 0.20, P ⬍ .05).
The MBP hyper-reactive group (the highest quartile [Q4]
of MBPR: n ⫽ 30) had significantly higher LV mass index
than the nonreactive group (the other quartiles [Q1 to 3]:
n ⫽ 90) (140 v 113 g/m2, P ⬍ .001). Even after controlling
for age, body mass index, gender, and 24-h systolic BP,
the MBP hyper-reactive status still remained a strong
predictor for LV hypertrophy.
Conclusions: Exaggerated MBPS, adjusted for physical activity, is associated with cardiac hypertrophy independent of ambulatory BP level in a community-dwelling
population. Am J Hypertens 2005;18:1528 –1533 © 2005
American Journal of Hypertension, Ltd.
Key Words: Morning blood pressure surge, morning
blood pressure reactivity, left ventricular hypertrophy,
physical activity, ambulatory blood pressure.
ll types of cardiovascular complications, such as
myocardial infarction, sudden cardiac death, ventricular fibrillation, ventricular tachyarrhythmia,
and stroke, have higher incidences in the early morning.1,2
In spite of the clinical importance of this phenomenon, the
mechanism accounting for the higher incidence of cardiovascular events in the morning remains unclear. Ambulatory blood pressure (BP) exhibits significant diurnal
variation subject to modification by various psychologic
and physical stimuli during daily life.3,4 Some studies have
suggested that several factors, such as BP increase in the
early morning (morning BP surge), augmented sympa-
A
thetic nerve activity, increase of coronary artery tonus,
increase in plasma catecholamines and cortisol concentration, aggregation of platelets, hypercoagulability, and decrease in fibrinolytic activity, could contribute to increase
cardiovascular events in the morning.5–7 Thus, morning
hypertension and exaggerated BP variability in the morning may be more closely associated with cardiovascular
risk than hypertension and BP variability during other
periods.8 –10 We have recently found that morning BP
surge is associated with the risk of stroke independent of
24-h BP level in hypertensive patients.11 In older hypertensive patients, morning BP surge, particularly that due to
Received March 16, 2005. First decision June 16, 2005. Accepted June
18, 2005.
From the Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical School, Tochigi, Japan.
This study was supported by a Research Grant for Cardiovascular
Medicine (14-6) from the Ministry of Health, Labor and Welfare (KK),
and a Research Grant (C-2) from the Ministry of Education, Science and
Culture (KK), Japan.
Address correspondence and reprint requests to Dr. Kazuomi Kario,
Division of Cardiovascular Medicine, Department of Medicine, Jichi
Medical School, 3311-1Yakushiji, Minamikawachi, Kawachi, Tochigi,
329-0498, Japan; e-mail: [email protected]
0895-7061/05/$30.00
doi:10.1016/j.amjhyper.2005.06.015
© 2005 by the American Journal of Hypertension, Ltd.
Published by Elsevier Inc.
AJH–December 2005–VOL. 18, NO. 12
␣-adrenergic activity, is closely associated with silent cerebrovascular disease.12 Previous reports also indicated
that morning BP surge is associated with cardiac hypertrophy and increased QTc dispersion independent of the
24-h BP level in hypertensive patients.13–15
Because morning BP surge predominantly starts after
awakening, physical activity after awakening is thought to
be a main contributing factor for morning BP surge.16 On
the other hand, the degree of morning BP surge adjusted
for physical activity, morning BP reactivity, may be associated with target organ damage. There have been no
reports that investigated the correlation between morning
BP surge adjusted for physical activity and hypertensive
target organ damage. Therefore, we used ambulatory BP
monitoring (ABPM) together with actigraphy, which
could identify the precise waking time and could quantitatively assess physical activity after arising, to study the
relationship between morning BP surge and hypertensive
target organ damage in relation to physical activity.
MORNING BP SURGE AND CARDIAC HYPERTROPHY
1529
Table 1. Characteristics of the study group
Total
Number
Age (yr)
Male, n (%)
Smoker, n (%)
Dyslipidemia, n (%)
Diabetes mellitus, n (%)
Clinic systolic BP (mm Hg)
Clinic diastolic BP (mm Hg)
24-h systolic BP (mm Hg)
24-h diastolic BP (mm Hg)
Sustained hypertension, n (%)
Morning systolic BP (mm Hg)
Morning systolic BP surge (mm Hg)
Morning BP reactivity (mm Hg/G0.5)
Morning physical activity (G)
Left ventricular mass index (g/m2)
Intima–media thickness (mm)
120
61 ⫾ 11
56 (47)
15 (13)
43 (36)
5 (4)
135 ⫾ 20
84 ⫾ 11.1
124 ⫾ 15.0
75 ⫾ 8.9
49 (40.8)
129 ⫾ 18
27 ⫾ 13
18 ⫾ 11
2.9 ⫾ 1.6
120 ⫾ 32
0.69 ⫾ 0.16
BP ⫽ blood pressure.
Data are shown as mean ⫾ SD or number (percentage).
Methods
Subjects
The study subjects were participants in a specific cardiovascular annual health examination performed in the community-based residents aged 20 years or older in Miyori
district in Kinugawa, Japan, in 1998. A total of 181 adults
(33% of 541 residents aged 20 years or older) gave their
informed consent and participated in this study.17 This
study was approved by the Research Ethics Committee,
Department of Cardiology, Jichi Medical School, Japan.
We selected the study patients according to the following
exclusion criteria: 1) those under antihypertensive therapy
during the 2-week period before the examination, 2) those
whose echocardiography findings could not be obtained
clearly, 3) available number of BP measurements during
ABPM ⬍80% of total measurements, and 4) those who
complained of severe sleep impairment due to ABPM. The
final subjects consisted of 120 patients (56 men and 64
women, mean age 61 years) (Table 1). None of these study
subjects overlapped with study subjects examined in our
previous study on morning BP surge.11 Clinic BP was
measured after resting in a sitting position for 5 min by
standard cuff methods.
24-h ABPM
Noninvasive ABPM was performed with an automatic
device (TM2420, A & D Co. Inc., Tokyo, Japan), which
recorded BP and heart rate every 30 min during both the
awake period and sleep. The ambulatory data used in the
present study were obtained by the oscillometric method.
Each subject was asked to remain as motionless as possible each time the monitor took a reading during waking
hours.
Normotension was determined when 24-h systolic BP
was ⬍130 mm Hg and diastolic BP was ⬍80 mm Hg, and
sustained hypertension was determined when 24-h systolic
BP was ⱖ130 mm Hg or diastolic BP was ⱖ80 mm Hg.
The subjects consisted of 71 normotensives and 49 untreated hypertensives diagnosed on the basis of ABPM.
We defined morning BP surge (MBPS) as the average
of systolic BPs during the 2 h after awakening minus the
average of systolic BPs during the 1 h that included the
lowest sleep BP (Fig. 1). This definition was the same as
that used in our previous study,11 whose study population
had no overlap with the present study population.
We classified the patients according to the percentage
of nocturnal systolic BP reduction (100 ⫻ [1 ⫺ Sleep
systolic BP/Awake systolic BP]) as follows: extreme dippers if the nocturnal systolic BP reduction was ⱖ20%;
dippers if the decrease was ⱖ10% but ⬍20%; nondippers
if the decrease was ⱖ0% but ⬍10%; and risers if it was
⬍0%.18,19
Actigraphy
The ABPM device was equipped with an actigraph, which
recorded the frequency of physical movement in two spatial axes. Physical activity was assessed continuously and
recorded in 60-sec epochs throughout the 24-h period. The
precise clock time of arising from bed was determined
from the individual’s diary and actigraph. In the case the
arising time was disagreed between diary and actigraphy,
we used the arising time written in each diary.
The morning physical activity of each subject was
defined as the sum of the activity in the 2 h after the arising
time. As the association between physical activity and BP
shows the best fit when the square root transformation is
applied to the activity measures,20 we calculated the morning BP reactivity (MBPR) as the ratio of MBPS/(Sum of
the 2-h activity after the arising time)0.5 (Fig. 1). Of
1530
MORNING BP SURGE AND CARDIAC HYPERTROPHY
AJH–December 2005–VOL. 18, NO. 12
area, as described previously.17 Images of right and left
common carotid arteries were obtained using a 7.5-MHz
transducer. Measurement of intima–media thickness
(IMT) of the far wall at the end-diastole was performed in
B-mode, and the IMT value was defined as the mean of
three measurements for both the left and right sides as
described previously.17
Statistical Analysis
FIG. 1. Definition of morning blood pressure (BP) surge and reactivity.
subjects with equivalent magnitude of BP surge, those
subjects with lesser degree of activity will have greater
MBPR. We classified the patients according to the level of
MBPR into four groups. The highest quartile (Q4) of
MBPR was defined as the morning BP hyper-reactive
group (n⫽30) and the other quartiles (Q1 to 3) as the
morning BP nonreactive group (n ⫽ 90).
Echocardiography
The M-mode echocardiography was performed with twodimensional monitoring just before attaching the ABPM
device. Left ventricular mass index (LVMI) was calculated from Devereux formula21 indexed to body surface
The unpaired Student t test and ␹2 test were used to test
differences between the two groups in the mean values of
continuous measures and prevalence rates. Pearson’s correlation coefficients were used to examine the relationships
among continuous measures. One-way analysis of variance (ANOVA) and of covariance (ANCOVA) (for controlling age and 24-h systolic BP) were performed to
detect differences among groups. Tukey’s honestly significant differences test was used for multiple pairwise comparisons of means among groups. Multiple logistic
analysis was performed to estimate and test the independent effects on LVMI of various measures, including
MBPR, 24-h systolic BP, age, and body mass index
(BMI). The statistical calculations were performed with
SPSS II (SPSS Inc., Tokyo, Japan). Differences/associations with P ⬍ .05 were considered to be statistically
significant.
Results
Correlations Between
Morning BP Reactivity, Clinic, or
24-h BP, Pulse Rate, and BP Variability
Table 2 shows the associations of MBPS and MBPR with
clinic or 24-h systolic and diastolic BPs, and pulse rate.
Age, clinic BPs, and 24-h BPs were significantly correlated with MBPR. On the other hand, there were no
significant correlations between 24-h pulse rate and
Table 2. Correlations of morning blood pressure surge and reactivity with cardiovascular remodeling in total
subjects
Morning BP Surge
Parameter
r
Age
Clinic systolic BP
Clinic diastolic BP
24-h systolic BP
24-h diastolic BP
24-h pulse rate
SD of 24-h systolic BP
SD of awake systolic BP
Left ventricular mass
index
Intima–media thickness
0.024
0.227
0.231
0.399
0.308
0.153
0.506
0.286
0.162
0.001
Abbreviation as in Table 1.
Pearsons correlation coefficients are shown.
P
Morning BP Reactivity
r
P
.792
.013
.011
⬍.001
.001
.094
⬍.001
.001
0.244
0.405
0.279
0.439
0.252
0.016
0.373
0.198
.007
⬍.001
.002
⬍.001
.005
.866
⬍.001
.030
.077
.997
0.296
0.122
.001
.183
AJH–December 2005–VOL. 18, NO. 12
MORNING BP SURGE AND CARDIAC HYPERTROPHY
1531
Cardiac and Vascular Remodeling
FIG. 2. Morning blood pressure surge or reactivity and hypertensive cardiac remodeling. Left ventricular mass index (LVMI) examined by echocardiography. We classified the patients into four
groups according to the level of morning BP surge or reactivity, the
lowest quartile (Q1) to highest quartile (Q4).
MBPR. The MBPR had positive relationships with 24-h
BP variability (SD of BPs during 24-h period) and awake
BP variability (SD of BPs during the awake period).
Relationships With
Nocturnal BP Decreases
Because the definition of MBPS is related in part to the
nocturnal BP decrease, we also studied the influence of
nocturnal BP dipping status. The prevalence of extreme
dippers, dippers, nondippers, and risers was not significantly different between the hyper-reactive group (10%,
63%, 27%, 0%, respectively) and the nonreactive group
(3.3%, 63%, 32%, 1.1%, respectively). The nondippers
(nondippers ⫹ risers: n ⫽ 38) tended to have higher LVMI
than dippers (extreme dippers ⫹ dippers: n ⫽ 82) in the
total sample (124 ⫾ 34 v 117 ⫾ 31 g/m2), however, the
difference was not statistically significant. There was no
significant difference in the IMT between the dippers and
nondippers (0.69 ⫾ 0.13 v 0.68 ⫾ 0.17mm, P ⫽ not
significant).
Table 2 also shows the associations of MBPS and MBPR
with cardiovascular parameters. In all the subjects studied
(n ⫽ 120), MBPR was significantly positively associated
with LVMI (r ⫽ 0.30, P ⫽ .001). The association between
MBPS and LVMI was not statistically significant (r ⫽
0.16, P ⫽ .08). There were no significant relationships
between MBPS or MBPR and IMT. The arising-associated
BP surge defined as the increase from the 2-h average BP
value just before getting up to the 2-h average BP values
after arising was not significantly associated with LVMI or
IMT (data not shown).
The morning BP hyper-reactive group had significantly
higher LVMI than the nonreactive group (140 v 113 g/m2,
P ⬍ .001) (Fig. 2). The cutoff value for identifying the
group with the highest reactivity was 23.2 mm Hg/G0.5.
On the other hand, the difference in LVMI between the
highest quartile of MBPS (Q4) and the lower quartiles (Q1
to 3) was not significant (129 v 117 g/m2, P ⫽ .07). The
morning BP hyper-reactive group was older (65 v 59
years, P ⫽ .02) and had higher 24-h BP (systolic: 133 v
121 mm Hg, P ⬍ .001; diastolic: 78 v 74 mm Hg, P ⬍ .05)
than the nonreactive group (Table 3). Even after controlling for age and 24-h systolic BP, the morning BP hyperreactive group still had significantly higher LVMI than the
nonreactive group (132 v 115 g/m2, P ⫽ .01). The prevalence of morning hyper-reactive group was significantly
higher in the sustained hypertension group (diagnosed by
ABPM) than in the normotensive group (38.8% v 15.5%,
P ⫽ .005).
Furthermore, morning hyper-reactive status was a significant determinant for left ventricular hypertrophy
(LVH) (LVMI ⬎125 g/m2) (Fig. 3). After adjusting for
24-h BP, age, sex, and BMI, the morning hyper-reactive
status remained a significantly strong predictor for LVH.
There were significant associations between 24-h BP
variability (r ⫽ 0.228, P ⫽ .01) and awake BP variability
Table 3. Characteristics of morning blood pressure reactivity subgroup
Number
Age (yr)
Male, n (%)
Sustained hypertension, n (%)
24-h systolic BP (mm Hg)
24-h diastolic BP (mm Hg)
24-h pulse rate (/min)
SD of 24-h systolic BP (mm Hg)
SD of awake systolic BP (mm Hg)
Abbreviation as in Table 1.
Data are shown as mean ⫾ SD.
* P ⬍ .05,
† P ⬍ .001 v non-reactive group.
Nonreactive
Group
Q1–3
Hyperreactive
Group
Q4
90
59 ⫾ 10
41 (46)
30 (33)
121 ⫾ 13
74 ⫾ 8
68 ⫾ 7
17 ⫾ 5
17 ⫾ 6
30
65 ⫾ 13*
15 (50)
19 (63)
133 ⫾ 17†
78 ⫾ 10*
67 ⫾ 8
20 ⫾ 4*
19 ⫾ 4*
1532
MORNING BP SURGE AND CARDIAC HYPERTROPHY
Odds Ratio (95%CI)
0
1
2
3
4
5
10
1. Unadjusted
4.9 (2.0 – 12.0)
Highest morning BP reactivity
p=0.001
( ï 23.2 mmHg/G0.5 )
2. Adjusted
for age, sex, BMI, and 24-hr SBP
Highest morning BP reactivity
( ï 23.2 mmHg/G0.5 )
3.8 (1.4 – 10.6)
p=0.01
FIG. 3. The odds ratios and 95% confidence intervals for left ventricular hypertrophy by hyper-reactive status were calculated by
multiple logistic regression analysis. We used the following conventional risk factors as covariates: age, sex, body mass index (BMI),
and 24-h systolic BP (SBP).
(r ⫽ 0.204, P ⫽ .03) and the LVH. Even after adjusting
for 24-h BP variability (P ⫽ .004) or for awake BP
variability (P ⫽ .002), the MBPR remained a significant
predictor for LVH.
Discussion
In this study we found that the morning BP surge, adjusted
for physical activity, was associated with cardiac hypertrophy in a community-dwelling population. In previous
studies, which found that morning BP surge was an independent determinant of LVMI and of increased QTc dispersion, physical activity was not controlled for in the
analysis.13–15 In our previous study on a different population from that examined in the present study, LVH diagnosed by electrocardiography tended to be more common
in individuals with exaggerated morning BP surge than in
those with moderate morning BP surge,11 although the
difference between the two groups did not reach statistical
significance. The advantages of the present study were that
LVH was assessed using echocardiography and morning
BP surge was defined more precisely using actigraphy.
One of the advantages of the present study is the precise
determination of arising time, identified using actigraphy,
to define morning BP surge. In our previous study, because we did not have actigraphy data, we used only diary
documentation to identify the arising time.11 In the present
study, we determined the time of arising from bed by
considering actigraphy data together with the individual’s
diary rather than defining it as a fixed time, and therefore
the morning BP surge in the present study would be the
most accurate to examine the association with target organ
damage. Mansoor et al22 previously examined the effects
of actigraphy, diary, and fixed-time methods on the analysis of ambulatory BP. The actigraphic data of the ambulatory BP yielded results closer to those obtained with the
diary than the fixed-time method. They concluded that
researchers studying the early morning BP surge should
consider using either actigraphy or a diary rather than
fixed-time methods of analysis to identify times of awakening. Kuwajima et al13 also used an active tracer
equipped with an acceleration sensor to sense the start of
AJH–December 2005–VOL. 18, NO. 12
physical activity related to awakening, but not awakening
itself.
There is no consensus on the definition of the morning
BP surge. Previously, Kuwajima et al13 separated the
increase in systolic BP into two parts. The first part was
the increase in systolic BP from the lowest value for 3 h
before arising to the value upon getting up, and the second
part was the increase from the value upon getting up to the
maximum BP 3 h after arising. The increase in systolic BP
after getting up correlated more significantly with wall
thickness, LVMI, and A/E ratio (the ratio of the peak of
late diastolic filling and the peak of early diastolic filling)
than those measurements before getting up. Gosse et al15
reported that the morning BP surge defined as systolic BP
elevation on arising minus the last supine systolic BP
before arising was significantly associated with LVMI.
However, in our present study the arising-associated BP
surge defined as the increase from the 2-h average BP
value just before getting up to the 2-h average BP values
after arising was not significantly associated with LVMI or
IMT (data not shown). In the present study, we used the
same definition of morning BP surge that we used in our
previous study,11 whose study population had no overlap
with that in the present study. The morning BP surge was
defined as morning BP level (the 2-h average of BPs after
waking) minus the night-time lowest BP (the 1-h average
of BPs including the lowest BP during sleep).11 This
morning BP surge includes not only the magnitude of BP
increase accompanied with arising but also the magnitude
of BP increase from the night-time lowest BP to BP early
in the morning before arising. The latter may be related to
poor sleep quality in this period. Both surges may be
attributable to different mechanisms leading to hypertensive target organ damage and subsequent cardiovascular
events through different mechanisms. Further studies on
hypertensive target organ damage and cardiovascular
prognosis are necessary for the definition of morning BP
surge.
No previous studies investigated the relationship between morning BP surge adjusted for physical activity
(morning BP reactivity) and target organ damage. In the
present study, even after controlling for age and 24-h
systolic BP, both of which are significant determinants of
LVMI, MBPR was independently associated with LVH.
The MBPR is a measure of an individual’s morning BP
increase adjusted for an equal amount of morning physical
activity. Our results indicated that a person whose BP
increases more markedly with a given amount of activity
in the morning had more advanced cardiac remodeling.
Because there was no significant association between
morning physical activity and LVMI, chronic exaggerated
morning BP surge, as indicated by increased morning BP
reactivity, seems to be the predominant determinant of
cardiac remodeling.
The prevalence of morning hyper-reactive group was
significantly higher in the sustained hypertension group
than in the normotensive group, suggesting that BP might
AJH–December 2005–VOL. 18, NO. 12
more markedly increase with a given amount of activity in
hypertensives than that in normotensives, partly because
of impaired baroreceptor sensitivity and autonomic dysregulation. Because there was no significant association
between the relative surge in morning BP (morning BP
surge divided by 24-h BP level) and LVMI or with IMT,
the absolute value of morning BP variability may be a
more important determinant of cardiovascular overload.
In addition, there were significant associations between
MBPR and ambulatory BP variability, and between ambulatory BP variability and the LVH. Even after adjusting
for these ambulatory BP variabilities, MBPR remained a
significant predictor for LVH. Therefore, the present data
indicate that increased ambulatory BP variability may
contribute to worsening of LVH, but MBPR is an independent predictor for hypertensive cardiac remodeling.
However, there is the opposite possibility that the higher
BP reactivity is favored for a higher increase in the cardiac
output of a hypertrophied ventricle in the early stage of
hypertensive heart disease. Because hypertrophied ventricles do not always show higher cardiac output, especially
in eccentric hypertrophy, this possibility seems to be low.
We need a prospective study to clarify this possibility
before LVH develops.
Concerning the association between dipping status and
MBPR, the prevalence of extreme-dippers, dippers, nondippers, and risers were not significantlt different between
the hyper-reactive group and in the nonreactive group.
Therefore, we considered that morning BP surge adjusted
for physical activity is one of independent predictors for
LVH apart from nocturnal BP decreases.
We also investigated the relationship of MBPS or
MBPR with carotid IMT, a measure of vascular remodeling. This relationship was not examined in any previous
studies. In the present study, there was no significant
relationship between morning BP surge and IMT. Thus,
cardiac remodeling may be more susceptible to BP variability in the morning than vascular remodeling.
The reproducibility of morning BP surge parameters
including MBPR is important. However, as this study
subjects were community dwelling, we could not obtain
the ABPM data twice or more. In future study, the reproducibility of parameters of morning BP surge should be
evaluated.
In conclusion, morning BP surge contributes to ambulatory BP variability and might promote LVH. Furthermore, exaggerated morning BP reactivity, adjusted for
physical activity, is associated with cardiac hypertrophy
independent of ambulatory BP levels in a communitydwelling population.
MORNING BP SURGE AND CARDIAC HYPERTROPHY
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
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